Anti-human leukocyte antigen-DR (MHC class II) humanized monoclonal antibody, IMMU-114, suppresses human to bovine cellular responses

作者：Park Kyung Hwa; Sawada Tokihiko^*; Murakami Toru; Ishii Yasuo; Yasuo Mineko; Urakawa Manami; Aoyagi Yoshito; Fuchinoue Shohei; Kubota Keiichi

来源：Journal of Surgical Research, 2012, 178(1): 472-477.

DOI：10.1016/j.jss.2012.02.006

• IMMU-114
• MHC class II HLA-DR
• Humanized antibody

The effect of an anti-human leukocyte antigen-DR (MHC class II) humanized monoclonal antibody, IMMU-114, against the human to bovine cellular response was investigated. %26lt;br%26gt;Methods: Human peripheral mononuclear cells (PBMCs) were cocultured with inactivated self-PBMCs (Self), bovine PBMCs with control antibody (Xeno), or bovine PBMCs with IMMU-114 (IMMU-114). Cellular responses were investigated by thymidine incorporation assay, CFSE (carboxyfluorescein diacetate succinimidyl ester)-mixed lymphocyte reaction, and cytokine production in culture medium. %26lt;br%26gt;Results: Thymidine incorporation rates at a 1:1 responder to stimulator ratio for Xeno + control antibody, Xeno + IMMU-114, Self + control antibody, and Self + IMMU-114 were 14201.3 +/- 1968.4, 513.0 +/- 49.5, 952.7 +/- 128.7, and 423.3 +/- 138.8 cpm, respectively (P = 0.032). Those at a 1:2 ratio were 6518.0 +/- 690.1, 896.6 +/- 92.9, 1051.0 +/- 123.6, and 736.0 +/- 35.6 cpm, respectively (P = 0.036). CFSE-mixed lymphocyte reaction demonstrated that the frequencies of CFSE-low, CD4(+), and CD25(+) activating T cells in Self, Xeno, and IMMU-114 were 0.27 +/- 0.04%, 3.65 +/- 0.53%, and 1.23 +/- 0.15%, respectively (P = 0.027). Cytokine production in culture medium indicated that IMMU-114 decreased Th1-type cytokines, including interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. %26lt;br%26gt;Conclusion: IMMU-114 effectively suppresses human to bovine cellular responses. The mechanism involves direct inhibition of the interaction between class II human leukocyte antigen-DR-positive cells and CD4(+) T cells, and indirect suppression of Th1 cytokine production.

• 出版日期2012-11